As the therapies for malignancy, in addition to surgical treatment, radiotherapy, and chemotherapy, there has been attempted immunotherapy which aims at obtaining therapeutic effect by enhancing the immune function of host patients. However, most of the immunotherapy procedures practically used thus far have obtained the effect by non-specifically enhancing immunecompetence of host patients, and drugs capable of inducing complete cure of tumors in clinical cases have not been practically used yet.
Many researchers have conducted investigations utilizing animal tumor models mainly based on mice to develop a drug capable of completely curing tumors. As a result, it has been clarified that tumors may be completely cured by efficiently inducing antigen specific immune responses, in particular, inducing cytotoxic T cells (CTLs), against tumor-associated antigens or tumor specific antigens expressed on various tumor cells. In order to treat tumors by such CTL induction, it is essential to elucidate an amino acid sequence of protein recognized by tumor specific CTL and a DNA sequence encoding the protein for each tumor.
In recent years, also for clinical tumors, it has been attempted to identify an antigen inducing tumor specific CTL and a DNA encoding the antigen, and utilize them for therapy.
Based on such conception, tumor antigen proteins capable of inducing CTL and DNAs encoding such proteins have been searched for. However, those identified so far are limited to the proteins such as those of MAGE family (T. Boon et al., Immunology Today, 18, 267–278, 1997), Mart-1, Thyrosinase, gp100 (S. A. Rosenberg, Immunology Today, 18, 175–182), which are the tumor antigens present in melanoma, and DNAs encoding them, and the proteins present in epidermoid cancer (derived from human head and neck cancer, CASP-8, J. Exp. Med., 186, 785–793, 1997) and DNAs encoding them.
On the other hand, as for digestive tract cancers including gastric cancer, the presence of a tumor antigen peptide which can induce CTL has been identified by the present inventors (Japanese Patent Unexamined Publication [KOKAI] No. Hei 9-151200/1997) However, it has not been clarified at all what kind of protein from which tumor peptide is derived, and much less structure of DNA encoding the tumor antigen protein.